Case Report: Disseminated hydatid cyst: Unusual presentation and therapeutic challenges

Introduction: Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato, is a parasitic disease prevalent in endemic regions. CE frequently leads to the formation of hydatid cysts in various organs, with the liver being the most commonly affected site. Involvement of the spleen has been rarely reported in the literature. Managing disseminated hydatid cyst disease presents significant diagnostic and therapeutic challenges. Case presentation: A 40-year-old female with a past medical history of hypothyroidism presented with sudden onset shortness of breath, dry cough, and chest pain for 3 days. She had a recent travel history to Egypt. Physical examination revealed mild right upper quadrant tenderness. Laboratory findings showed elevated white blood cell count with eosinophilia and increased inflammatory markers. Chest X-ray and pan-computed tomography (Pan-CT) scans identified multiple cystic lesions in the lung, liver and spleen. Serological tests confirmed the presence of anti-Echinococcus antibodies, leading to a diagnosis of disseminated hydatid cyst disease. The patient was managed medically and surgically by a multidisciplinary team. Conclusion: Disseminated hydatid cyst disease, though rare, presents complex diagnostic and management challenges. Timely recognition, supported by clinical, radiological, and serological assessments, is essential. Surgical intervention should be considered in a patient when multiple extrahepatic cysts are present, and rupture is evident, as this approach can significantly reduce patient morbidity and mitigate life-threatening complications.


Introduction
The hydatid disease, cystic echinococcosis (CE), is a parasitic disease caused by Echinococcus granulosus sensu lato.
In endemic countries, CE shows an average incidence of 200 per 100,000 populations with a mortality range of 2-4% when appropriate treatment is provided promptly. 1The larval form of the deadly tapeworm may lodge itself in various different sites and organs to form fluid-filled sacs known as hydatid cysts.The disease may manifest through dysfunction of the organs where the cysts form.With the liver being the most vulnerable, it alone accounts for nearly 70% of cases, while the lungs account for 20% of deposits.Other organs may also be involved in other rarer cases, including the kidneys, muscles, brain, and spleen. 2 In this case, we are reporting a 40-year-old female patient that presented to the hospital with sudden onset shortness of breath, a dry cough, and chest pain for only 3 days.Radiological reports showed hydatid cyst involvement of the liver, the lungs, and the spleen, with positive antibodies on serological studies.She was diagnosed as a case of disseminated hydatid cyst and managed by a multidisciplinary team.

Case presentation
A 40-year-old Egyptian female, previously diagnosed with hypothyroidism and currently taking thyroxine, presented to the hospital with sudden onset shortness of breath, a dry cough, and chest pain for 3 days.The patient denied any orthopnea or paroxysmal nocturnal dyspnea.The review of other systems was unremarkable.Apart from thyroxine, the patient was not taking any other medications.She had traveled to Egypt two months before her presentation.In the emergency department, her vital signs were within normal limits.Her temperature was 36.7°C,her blood pressure was 136/72 mmHg, and she had a heart rate of 86 beats per minute, all while maintaining normal saturation on room air.On physical examination, she was in distress; auscultation of her chest was clear with no crackles or rhonchi.An abdominal examination revealed only minor tenderness in the right upper quadrant.Examination of other systems was unremarkable.Results of her lab investigations revealed a high white blood cell (WBC) count of 12,000 cells/μl (normal range=4,000-11,000 cells/μl) with prominent eosinophils at 3.5 cells/μl (normal range=0-0.5cells/μl) and elevated C-reactive protein level of 25 mg/L (normal range= 0-5 mg/L).Initial impression was either heptic hydatid cyst or hepatic granuloma.
A chest X-ray showed multiple well-defined radiopaque rounded densities (Cannon balls) scattered throughout both lungs and more on the right side (Figure 1).

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The radiologist recommended a pan-computed tomography (PAN CT) scan to look for cystic involvement on other organs, which revealed multiple large, well-circumscribed bilateral pulmonary cystic lesions representing hydatid cysts.The largest cyst measured 6 cm in the anterior segment of the right upper lobe.In the posterior basal region of the left lobe, a ruptured hydatid cyst with surrounding consolidation was discovered.Furthermore, multiple enlarged, variable-size subcapsular cystic lesions with multiple curvilinear hyperattenuating structures were seen in both lobes of the liver.The largest is a 5-cm-segment V/VI image with no postcontrast enhancement.A 7.5-cm-enhancing cystic lesion in the upper pole of the spleen was also seen (Figure 2).
The image findings supported the diagnosis of disseminated hydatid disease, and serological tests for echinococcus antibodies were positive.Urgent consultations were obtained with both the infectious disease and thoracic surgery teams.The infectious disease (ID) team recommended 400 mg of albendazole orally twice daily with follow-up until resolution.The thoracic surgery team advised her to return to the clinic after two weeks of stabilization for elective surgery and to consult with hepatobiliary surgeons for liver and spleen cysts.The plan was to surgically remove the lung cysts first, followed by the liver and spleen cysts later, along with albendazole, which was prescribed by the ID team.After three days of stabilization and resolution of symptoms, the patient was discharged with an outpatient follow-up with the infectious disease, thoracic surgery, and hepatobiliary surgery teams.One week after being discharged, the patient returned with a severe dry cough and chest pain.A new CT scan of the chest revealed that a new cyst had ruptured in the right upper lobe of the lung (Figure 3).The patient underwent an emergency thoracotomy with multiple cystectomies, and histopathological examination of the surgical specimen revealed findings consistent with hydatid cysts.Six months later, a follow-up CT scan of the chest showed cyst resolution.The patient had a successful laparoscopic deroofing and endocystectomy of hepatic and splenic cysts one month later, and the pathological analysis of the surgical specimen from hepatic and splenic tissues showed findings consistent with a hydatid cyst.

Discussion
Hydatid cysts are categorized as zoonotic infections that primarily affect dogs, which serve as definitive hosts when they consume contaminated sheep, goats, or various animal tissues.A single cyst can contain numerous protoscolices, each capable of maturing into an adult tapeworm upon ingestion by the definitive host.Animals acquire this infection through the consumption of contaminated food.In humans, accidental intermediate hosts become infected through the consumption of infected food or water, contact with contaminated soil, or direct contact with definitive hosts.The larval stage enters the bloodstream and infiltrates various organs in the body, particularly those with high blood supplies. 3,4Echinococcus granulosus cysts can inhabit any anatomical site.The clinical manifestation depends on several factors, including the affected organ, specific location within the organ, stage of cyst development, and vitality of the cyst contents.In most cases, these cysts remain silent and are often discovered incidentally during routine imaging or postmortem examinations.However symptoms may arise as a result of cyst enlargement, causing pressure effect on adjacent structures, potential infection, or the rupture of cyst contents into adjacent body cavities. 5After infection, the parasitic infection can disseminate to different organs via the lymphatic or venous system, with the liver being the most frequently affected organ initially.Appropriate treatment reduces the risk of further spread. 6Our patient presented with a cough, shortness of breath, and chest pain due to a ruptured cyst.In addition to that, his physical examination showed right upper abdominal tenderness.
The diagnosis of a hydatid cyst can be established through combination of clinical assessment, laboratory and serological studies, radiological evidence, and histopathological analysis.In addition to identifying elevated inflammatory markers and a high eosinophil count in the bloodstream, serological tests of our patient also revealed the presence of anti-Echinococcus antibodies.A previous research study has proposed that eosinophilia in individuals afflicted with echinococcosis lacks specificity and has advocated for the inclusion of serological studies in the diagnostic process.These serological tests exhibit a sensitivity of 80% to 100% for hepatic echinococcosis, 50% to 56% for pulmonary echinococcosis, and 25% to 50% for detecting involvement of other organs. 7Generally, the classic radiological finding of a hydatid cyst of the lung is a well-defined oval to rounded opacity ranging from 1 to 20 cm in size.Usually, lung cysts are located in the lower lobes (60% of cases) and can be multiple and bilateral. 8In cases of hepatic involvement, the most common affected portion is the right portion of the liver.The third most common site of involvement, following the liver and the lung, is the spleen.Splenic hydatid cysts are relatively rare and usually solitary, and their imaging characteristics are similar to those of hepatic hydatid cysts. 9A previous study also reported a case of disseminated echinococcosis involving the lung, liver, and spleen with predominantly abdominal symptoms and pleural effusion on radiological studies. 10In our case, a chest X-ray was ordered, and it showed various rounded radiopaque densities, which prompted further evaluation by a pan-computed tomography (pan-CT) scan.The pan-CT results showed multiple cystic lesions in both lungs.The largest cyst was 6 cm in size and located on the left lobe, and a ruptured cyst on the right lobe was also noted.In addition to pulmonary cysts, multiple cystic lesions involving both lobes of the liver and spleen were also detected, supporting the diagnosis of disseminated echinococcosis.
The management of hydatid cysts is both medical and surgical.The indications for surgical intervention are a large cyst size of 10 cm, concomitant extrahepatic involvement, and an infected cyst. 11There are two types of surgical intervention: radical (pericystectomy) and conservative (partial cystectomy); the surgery type is usually determined based on the cyst's size and the presence of cysts outside the liver.In a systematic review, researchers compared the results of radical and conservative surgery with and without a course of chemotherapy postoperatively.The result of radical surgery followed by a course of antiparasitic medication has shown a better outcome in terms of length of hospital stay and post-surgical complications compared to conservative surgery.However, the time of radical surgery was longer with a larger amount of blood loss, and additionally, use of antiparasitic medication after surgery showed a better outcome with reduced recurrence regardless of the type of surgery. 12Albendazole is the standard medication for hydatid cysts, as recommended by the World Health Organization (WHO).It is prescribed both before and after surgery to reduce cyst size, prevent relapses, sterilize the cyst, and mitigate post-surgical complications. 13Our patient started first on medical treatment and planned for elective surgery by the cardiothoracic team, but because she developed symptoms a week after resuming medication after the rupture of an additional cyst, she underwent an urgent right thoracostomy with cystectomy, followed by histopathological analysis of the surgical specimen, which showed findings suggestive of a hydatid cyst.The patient was discharged on albendazole oral tablets.On her 6-month follow-up, a CT scan of the lungs showed evidence of resolution of the hydatid cyst.One month later, elective laparoscopic deroofing and endocystectomy for hepatic and splenic cysts were done, and the surgical specimen was investigated in the histopathology lab.The results showed findings consistent with a hydatid cyst.

Conclusion
Prompt suspicion and diagnosis of a ruptured hydatid cyst are vital, particularly in patients with respiratory symptoms and radiographic evidence of cystic lesions, especially in those originating from endemic regions.Early surgical intervention is strongly advised when multiple extrahepatic cysts are present, and rupture is evident, as this approach can significantly reduce patient morbidity and mitigate life-threatening complications.

Case report consent
Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.
The authors did not provide differential diagnosis for this case, both at initial presentation or in discussion part.
It would be better to include a histopathological specimen picture or slide demonstrating the hydatid cyst.

Is the case presented with sufficient detail to be useful for other practitioners? Yes
Competing Interests: No competing interests were disclosed.Although no standardized definition of disseminated hydatidosis exists, in our opinion the term should be limited to secondary echinococcosis, i.e. the dissemination of cyst following spillage and seeding of protoscoleces after leakage or rupture, spontaneous or otherwise typically in the peritoneal or pleural cavities.By this definition, this patient would have multi-organ echinococcosis instead, because the cysts are all intra-parenchymal.In lung CE the risk of cyst rupture is higher than in the liver with potential complications such as bronchial and pleural 1 .The first chest CT of the patient showed the rupture of one lung cyst into the pleural space with pericystic consolidation.Complicated lung hydatid disease can be dangerous, even deadly (anaphylaxis, asphyxia) and, for this reason, early treatment is essential.The authors correctly based their hypothesis on clinical picture, imaging findings and serology.However, serology only has a confirmatory role and a negative serology does not rule out echinococcosis.Indeed, CE diagnosis is mainly made through imaging.The positive serology can be explained by the presence of multiple cysts with rupture, factors increasing serology sensitivity in the lung.We are interested in knowing which type of serologic test has been used.After diagnosis, the patient was treated with albendazole (ABZ) and the thoracic surgical team suggested to defer surgery to completion of two weeks of medical therapy.Therefore, the woman was discharged and a week later presented again to the E.D. with the rupture of one contralateral lung cyst.We argue that the patient should have been operated immediately at first presentation, without delay.Cysto-pleural fistula poses risk of pleural dissemination and disease relapse and would have required immediate thoracoscopic pleural toilette with protoscolicidal agents (hypertonic solution, iodopovidone), under ABZ prophylaxis (starting the day before the procedure).As second step, the intact right lung cysts could be removed (immediately after stabilization, i.e. one week later).The use of ABZ in the lung is controversial: in uncomplicated lung CE, starting ABZ is not urgent since the risk of treatment-induced cyst rupture (cyst membrane detachment and opening of cysto-bronchial fistula), while it is indicated as peri-operative prophylaxis 1 .In the present case, the patient had complicated disease with pleural fistula and required ABZ to prevent the larval spillage (secondary echinococcosis), but in so doing the other lung uncomplicated cysts were damaged by medical therapy and ruptured, requiring emergency surgery.We guess that a close monitoring of the patient without interrupting hospitalization would have been more beneficial for such complications.In the conclusion of their report, the colleagues state that "early surgical intervention is strongly advised when multiple extrahepatic cysts are present and rupture is evident", but questionably choose to discharge the patient with ABZ.It is likely that the second rupture may have been triggered by medical treatment.We agree with the authors in the choice of a sequential surgical approach prioritizing lung cysts: in multi-organ echinococcosis, due to the higher risk of complication of lung disease, thoracic surgery should be scheduled as quickly as possible and before handling abdominal disease.In some instances, i.e. parasitic cysts of the right liver with concomitant supradiaphragmatic lung cysts, same-time surgery (chest and liver) can be performed by experienced surgeons.Otherwise, surgery in two times is an acceptable option, unless in case of complicated abdominal cysts.The authors adequately chose a parenchymal-sparing technique, according to expert recommendations 12 .No information is given about the use of surgical field protection (pads soaked with hypertonic saline) and, more importantly, about the management of the left lung cyst complicated by rupture: as highlighted above, pleural fistula requires surgical toilette, otherwise the patient is at high risk of secondary echinococcosis.We are interested in knowing how did the authors deal with the left lung ruptured cyst.The authors said that the patient was discharged with oral ABZ after the first surgery for lung disease, but we did not find details about the timing of coverage and if the ABZ prophylaxis was used for the subsequent abdominal surgery: according to recommendations, a 1-3 months course of ABZ after each surgical act is required.Some remarks about the Introduction:

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Incidence of CE (number of new infections/year) is difficult to calculate because the disease lacks an acute symptomatic phase after infection and therefore can go unnoticed.The surrogate epidemiological parameter is the number of new diagnosis/year, based on symptomatic cases seeking medical care.Unfortunately, this measure does not reproduce the real burden of disease, because a great majority of CE cases are asymptomatic, hence not reported.

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We suggest to change the reference n.1 in relation with CE epidemiology and mortality rate, since the paper by Schweiger et al. is about alveolar echinococcosis (AE).The topic is well described in the review by Wen et al. 3 .

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In the discussion chapter: We would like to comment on the sentence "a single cyst can contain numerous protoscoleces": strictly speaking, a single hydatid fertile cyst contains hundreds to thousands of protoscoleces, as shown in studies carried out in the intermediate host 4 .

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A more accurate description of the definitive host infection should be given: canids acquire the metacestode through ingestion of parasitized viscera of the intermediate host.

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Conversely surgery is the only treatment for lung CE with prompt partial cystectomy as first option 5 .
In the colleague's paper no information about the cyst stage is available and this point is noteworthy and should be addressed because it is crucial for choosing the treatment.Apparently, an ultrasound examination of liver and splenic cysts has not been performed, hence cysts stage is lacking.
In this case, if abdominal cysts were active cysts (CE1 stage), they could have potentially been treated with medical or percutaneous treatment, turning to surgery once conservative therapy had failed.We read that laparoscopic endocystectomy was performed on liver and splenic cysts.It would be useful to share details of the procedure on the spleen: was spleen removed together with the cyst?Spleen-sparing surgical options need to be considered because splenectomized patients are at significant risk of infection, with overwhelming post-splenectomy sepsis (OPSI) as the most serious complication (vulnerability to invasive infections by encapsulated bacteria: S. pneumoniae, H. influenzae, N. meningitidis).Prevention with vaccination against such pathogens is recommended 7 .Finally, it would be useful to know if clinical and radiological follow-up is planned: if available, we would appreciate to evaluate imaging of lungs and abdomen after surgery.
by this case report.In case presentation, the authors should write the events as a scenario by periods of time.They should give more details about radiological examinations because radiological examinations are the the clue for diagnosis of hydatid cysts, and usually pathognomonic for hydatid cyst.The authors should add CT image of chest with mediastinal window to show the contents of the fluid cysts.It is better to add abdominal ultrasound images for liver and splenic cysts if available.They should give wider area for the radiological methods of diagnosis of hydatid cyst.

2.
In discussion, the authors should compare their findings with previous similar results either in radiological findings or in surgical intervention and outcomes.

3.
Other minor corrections such as adding units of WBCs and others are needed.4.
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Figure 2 .
Figure 2. Axial and coronal selected images.(A) Well-circumscribed bilateral pulmonary cystic lesions representing hydatid cysts.The largest cyst measured 6 cm in the anterior segment of the right upper lobe.(B) Bilateral multiple cysts.(C) Ruptured hydatid cyst with surrounding consolidation in the posterior basal region of the left lobe.(D) Multiple enlarged, variable-size subcapsular cystic lesions with multiple curvilinear hyperattenuating structures in both lobes of the liver.The largest is a 5-cm-segment V/VI image with no postcontrast enhancement.A 7.5cm-enhancing cystic lesion in the upper pole of the spleen.

Figure 3 .
Figure 3. CT scan of the chest.Ruptured cyst in the right upper lobe of the lung.

Figure 4 .
Figure 4. Multiple selected axial and coronal images of the abdomen and chest showing multiple cysts with average Hounsfield unit value of around zero indicating the fluid content.

Reviewer Report 13
February 2024 https://doi.org/10.5256/f1000research.155570.r234518© 2024 D'Alessandro G et al.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Gian Luca D'Alessandro Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy Pietro Rinaldi 1 Division of Thoracic Surgery, Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo Alessandria, Alessandria, Piedmont, Italy 2 Department of Molecular Medicine, University of Pavia, Pavia, Lombardia, Italy In the case reported by A. M. Babiker et al. the patient, an Egyptian woman aged 40 y.o., sought medical attention for respiratory symptoms and multiple parenchymal cystic lesions: 3 in the right lung, 1 in the left lung, at least 3 in the liver and 1 in the spleen.Respiratory symptoms (shortness of breath, cough and chest pain), radiological picture, eosinophilia and positive E. granulosus serology suggested the diagnosis of multi-organ CE complicated by rupture of the left lung cyst.
In liver CE and broadly speaking in abdominal CE, surgery is not necessarily the best option and should be based primarily on a stage-specific approach, as per WHO recommendations 1 :CE1 and CE3a liver cysts do not need necessarily need surgery and can be managed with ABZ or with percutaneous treatments, according to their size; ○CE is not a frequent cause of eosinophilia, but when eosinophilia is detected in a patient from an endemic area, CE should be considered as eosinophilia suggests leakage or rupture6.○Treatment of CE is complex and indications are different in lung and liver disease.○ Complicated liver cysts (i.e.biliary fistula, infected cysts) require surgery.